HCC Hepatocellular carcinoma (HCC) is an increasing pubic health problem in the United States. The Mount Sinai Hospital in New York has become a major referral center for this disease, with 231 new patients with HCC or suspected HCC first seen in 2000. Myron Schwartz, MD (the applicant) is Associate Professor of Surgery, Deputy Director of Liver Transplantation, and Chief of Hepatobiliary Surgery at Mount Sinai. Dr. Schwartz has proven record of patient-oriented research (POR), with 156 peer-reviewed publications, and a long history of mentoring trainees who go on to successful careers in academic surgery, including 7 who are now directors of transplant programs. Dr.Schwartz's clinical and academic focus is on HCC, and he is an internationally recognized expert on HCC care. The central hypothesis of this proposal is that a program which seamlessly incorporates clinical care and POR will maximize quality of care, provide unparalleled research opportunities, and create an ideal setting for the training of clinician/researches. Dr.Schwartz's role is as director of the program, principal investigator for surgery-related projects, and mentor for trainees. The specific aims are to conduct projects exploring: 1. Etiology-" Gene Expression Profiles in HCC"; 2.Diagnosis-"Utility of AFP-L3% in Screening, Diagnosis, and Prognosis of HCC";3. Secondary prevention after resection- "Prevention of HCC Recurrence after Surgical Resection by Vaccination with Tumor-Derived Heat Shock Protein gp96 and Associated Peptides"; 4. Secondary prevention after transplantation- "Sirolimus vs Tacrolimus as the Primary Immunosuppressive Agent after Liver Transplantation for HCC"; and 5. "Treatment of unresectable HCC- "Cytokine Inhibition in HCC". Mount Sinai's commitment to furthering POR and education is reflected in the recent awarding by the NIH of a K30 institutional Clinical Research Curriculum Award, a T32 institutional Training Grant in Investigative Gastroenterology, and a K23 Mentored POR Career Development Award to a junior faculty member to study novel HCC therapies. This program provides a truly remarkable opportunity to make meaningful progress in understanding, preventing and treating HCC, while in the process providing fertile training ground for young physician-scientists.